Synthesis and evaluation of a novel 99mTc nitrido radiopharmaceutical with alendronate dithiocarbamate as a potential bone‐imaging agent

• Published in: Chemical biology & drug design 2018-02, Vol.91 (2), p.545-551
• Main Authors: Song, Xiaoqing, Wang, Yue, Zhang, Junbo, Jin, Zhonghui, Zhang, Weifang, Zhang, Yanyan
• Format: Article
• Language: English
• Subjects: 99mTc; alendronate; bone; dithiocarbamate; imaging
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.13117

Currently, a popular strategy for designing novel radioprobes as bone‐imaging agents is based on the concept of bifunctional radiopharmaceuticals. Considering the dithiocarbamate ligand can act as a suitable bifunctional linking agent to attach technetium‐99m (99mTc) to corresponding target molecules, in this study, alendronate dithiocarbamate (ALNDTC) was synthesized and radiolabeled with [99mTc≡N]2+ core by ligand exchange reaction to produce 99mTcN‐ALNDTC complex, for the potential use as a novel probe for bone imaging. The radiochemical purity of the complex was over 90%. The complex was stable in vitro and could bind to hydroxyapatite. The partition coefficient result indicated it was hydrophilic, and an evaluation of biodistribution in mice indicated that the complex exhibited a higher bone uptake than did 99mTc‐labeled methylenediphosphonate (99mTc‐MDP). Further, single photon emission computed tomography imaging study indicated clear accumulation in bone, suggesting that 99mTcN‐ALNDTC would be a promising candidate for bone imaging. 99mTcN‐ALNDTC exhibits high radiochemical yield, good in vitro stability, high bone uptake, rapid blood clearance, and clear bone single photon emission computed tomography image. All of these results supported the perspective that 99mTcN‐ALNDTC holds the potential for bone imaging.